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Mitophagy in neurodegenerative disease pathogenesis

neural Regeneration research 2024年第5期19卷 998-1005页

作者： Kan Yang Yuqing Yan Anni Yu Ru Zhang Yuefang Zhang Zilong Qiu Zhengyi Li Qianlong Zhang Shihao Wu Fei Li Department of Developmental and Behavioural Pediatric&Child Primary Care Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children’s Environmental HealthXinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Center for Excellence in brain science and intelligence technology Institute of NeuroscienceState Key Laboratory of NeuroscienceCAS Key Laboratory of Primate NeurobiologyChinese Academy of SciencesShanghaiChina College of Materials and Chemical Engineering Hunan Institute of EngineeringXiangtanHunan ProvinceChina School of Medicine Yunnan UniversityKunmingYunnan ProvinceChina Songjiang research institute Shanghai Jiao Tong University School of MedicineShanghaiChina Neurosurgery Department Kunming Yenan HospitalKunmingYunnan ProvinceChina

Mitochondria are critical cellular energy resources and are central to the life of the *** selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and *** neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional *** evidence indicates that mitophagy is pivotal to the pathogenesis of neurological ***,more work is needed to study mitophagy pathway components as potential therapeutic *** this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and *** then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological ***,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate ***,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral ***,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative ***,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis autophagy mitochondria mitophagy mitophagy receptor Parkin Parkinson’s disease PINK1

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Solid-state non-volatile memories based on vdW heterostructure-based vertical-transport ferroelectric field-effect transistors

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science China(Information sciences) 2024年第6期67卷 198-206页

作者： Qiyu YANG Zheng-Dong LUO Fei XIAO Junpeng ZHANG Dawei ZHANG Dongxin TAN Xuetao GAN Yan LIU Zhufei CHU Yinshui XIA Genquan HAN Hangzhou institute of technology Xidian University State Key Discipline Laboratory of Wide Band Gap Semiconductor technology School of MicroelectronicsXidian University School of Artificial intelligence Xidian University School of Materials science and Engineering University of New South Wales (UNSW) Sydney ARC centre of Excellence in Future Low-Energy Electronics Technologies (FLEET) University of New South Wales (UNSW) Sydney Key Laboratory of Light Field Manipulation and Information Acquisition Ministry of Industry and Information Technologyand Shaanxi Key Laboratory of Optical Information TechnologySchool of Physical Science and TechnologyNorthwestern Polytechnical University Faculty of Electrical Engineering and Computer science Ningbo University

Driven by the explosive development of data-centric computation applications, it is becoming urgent to develop in-memory computing devices that are beyond the von Neumann architecture with an arrangement of separated logic and memory components. The transistor-type solid-state non-volatile memories,such as ferroelectric field-effect transistors(Fe FETs), have long been regarded as a competitive candidate for future in-memory computing architectures. However, the density scaling towards high-density arrays would require advanced Fe FETs with reduced footprints, which remains a great challenge so far. Here, a vertical-transport(VT) Fe FET that flips the charge transport channel perpendicular to the substrate plane is proposed, in which a ferroelectric gate and a van der Waals(vd W) heterojunction channel are vertically integrated, effectively reducing the device footprints. The proposed VT-Fe FET shows not only the robust binary non-volatile memory states but also several key synaptic functionalities at the device level. An artificial neural network with supervised learning was simulated based on the device conductance switching properties,showing excellent classification accuracy for the MNIST handwritten digits. These findings suggest that the proposed VT-Fe FET could offer a new solution for future non-volatile memories as well as more advanced neuromorphic systems.

关键词： vdW heterostructure non-volatile memory vertical-transport transistor ferroelectric field-effect transistor memristive devices

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brain-inspired dual-pathway neural network architecture and its generalization analysis

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science China Technological sciences 2024年

作者： DONG SongLin TAN ChengLi ZUO ZhenTao HE YuHang GONG YiHong ZHOU TianGang LIU JunMin ZHANG JiangShe College of Artificial intelligence Xi'an Jiaotong University School of Mathematics and Statistics Xi'an Jiaotong University State Key Laboratory of brain and Cognitive science Institute of Biophysics Chinese Academy of Sciences institute of Artificial intelligence Hefei Comprehensive National Science Center University of Chinese Academy of sciences

In this study, we explored the neural mechanism of global topological perception in the human visual system. We showed strong evidence that the retinotectal pathway in the archicortex of the human brain is responsible for global topological perception, and for modulating the local feature processing in the classical ventral visual pathway. Inspired by this recent cognitive discovery,we developed a novel CogNet architecture to emulate the global-local dichotomy of human visual cognitive mechanisms. The thorough experimental results indicate that the proposed CogNet not only significantly improves image classification accuracies but also effectively addresses the texture bias problem observed in baseline CNN models. We have also conducted mathematical analysis for the generalization gap for general neural networks. Our theoretical derivations suggest that the Hurst parameter, a measure of the curvature of the loss landscape, can closely bind the generalization gap. A larger Hurst parameter corresponds to a better generalization ability. We found that our proposed CogNet achieves a lower test error and attains a larger Hurst parameter,strengthening its superiority over the baseline CNN models further.

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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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neural Regeneration research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National research Center for Physical sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina institute of Artificial intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular Cell sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina brain research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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Neuromorphic circuits based on memristors: endowing robots with a human-like brain

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Journal of Semiconductors 2024年第6期45卷 47-63页

作者： Xuemei Wang Fan Yang Qing Liu Zien Zhang Zhixing Wen Jiangang Chen Qirui Zhang Cheng Wang Ge Wang Fucai Liu School of Optoelectronic science and Engineering University of Electronic Science and Technology of ChinaChengdu 610054China Yangtze Delta Region institute(Huzhou) University of Electronic Science and Technology of ChinaHuzhou 313099China

Robots are widely used,providing significant convenience in daily life and *** the rapid development of artificial intelligence and neuromorphic computing in recent years,the realization of more intelligent robots through a pro-found intersection of neuroscience and robotics has received much *** circuits based on memristors used to construct hardware neural networks have proved to be a promising solution of shattering traditional control limita-tions in the field of robot control,showcasing characteristics that enhance robot intelligence,speed,and energy ***-ing with introducing the working mechanism of memristors and peripheral circuit design,this review gives a comprehensive analysis on the biomimetic information processing and biomimetic driving operations achieved through the utilization of neuro-morphic circuits in brain-like *** hardware neural network approaches,including digital-analog hybrid circuit design,novel device structure design,multi-regulation mechanism,and crossbar array,are summarized,which can well simulate the motor decision-making mechanism,multi-information integration and parallel control of brain at the hardware *** will be definitely conductive to promote the application of memristor-based neuromorphic circuits in areas such as intelligent robotics,artificial intelligence,and neural ***,a conclusion and future prospects are discussed.

关键词： neuromorphic devices neuromorphic circuits hardware networks memristors humanlike robots

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Emergence of machine language: towards symbolic intelligence with neural networks

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National science Review 2024年第4期11卷 27-30页

作者： Yuqi Wang Xu-Yao Zhang Cheng-Lin Liu Tieniu Tan Zhaoxiang Zhang State Key Laboratory of Multimodal Artificial intelligence Systems Institute of AutomationChinese Academy of Sciences

Representation learning is a core issue in artificial intelligence (AI). Currently,there exists a disparity in the choice of representation between humans and machines. Humans rely on discrete language for communicati...

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Microglial glutaminase 1 mediates chronic restraint stress-induced depression-like behaviors and synaptic damages

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Signal Transduction and Targeted Therapy 2024年第1期9卷 40-43页

作者： Huili Chen Shengyang Fu Xiangyu Li Meng Shi Jiazhen Qian Shu Zhao Ping Yuan Lu Ding Xiaohuan Xia Jialin C.Zheng Center for Translational Neurodegeneration and Regenerative Therapy Tongji Hospital affiliated to Tongji University School of Medicine200065 ShanghaiChina Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina Translational research institute of brain and brain-Like intelligence Shanghai Fourth People’s Hospital affiliated to Tongji University School of Medicine200434 ShanghaiChina

Dear Editor,Major depressive disorder(MDD)is one of the most common psychiatric illnesses that significantly increase the risk of suicide.1 Stress-triggered dysfunctions of microglia have been identified as a commonly occurred pathological feature of MDD.1–3 Microglial dysfunction contributes to the pathogenesis of MDD via immunoresponses/neuroinflammation-mediated neural damage and pathological synapse loss-mediated neural circuit disruption.1 Although the involvement of microglia in MDD has been widely investigated,the molecular mechanisms underlying microglial dysfunction remain largely ***,we identified glutaminase 1(Gls1)as one key protein that participates in microglial dysfunction.4–6 Gls1 catalyzes the hydrolysis of glutamine to produce glutamate in the brain.4 Besides its well-known role in excitatory neurotoxicity,we found Gls1 up-regulation in microglia in animal models of Alzheimer’s disease and ischemic stroke.4,7 Gls1 activates microglia to overproduce cytokines and release inflammatory extracellular vesicles,therefore leading to neuroinflammation in animal models of Alzheimer’s disease and ischemic stroke.4–6 More importantly,Gls1 has been found to be up-regulated in the brains of MDD patients,and microglial Gls1 deficiency mitigated LPS-induced depression-like behaviors.8 However,LPS exposure is not an appropriate model to mimic MDD phenotypes,leaving the involvement of Gls1 in MDD an undetermined question.

关键词： involvement inflammation media

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A Bio-Inspired Integration Model of Basal Ganglia and Cerebellum for Motion Learning of a Musculoskeletal Robot

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Journal of Systems science & Complexity 2024年第1期37卷 82-113页

作者： ZHANG Jinhan CHEN Jiahao ZHONG Shanlin QIAO Hong State Key Laboratory of Multimodal Artificial intelligence Systems Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Artificial intelligence University of Chinese Academy of SciencesBeijing 100049China.

It is a significant research direction for highly complex musculoskeletal robots that how to develop the ability of motion learning and *** cooperations of multiple brain regions are crucial to improving motion *** by the neural mechanisms of structures,functions,and interconnections of basal ganglia and cerebellum,a biologically inspired integration model for motor learning of musculoskeletal robots is *** on the neural characteristics of the basal ganglia,the basal ganglia actor network,which mainly simulates the dorsal striatum,outputs motion commands,and the basal ganglia critic network,which simulates the ventral striatum,estimates actionstate *** network parameters are updated using the soft actor-critic *** on the sensorimotor prediction mechanism of the cerebellum,the cerebellum network evaluates the state feature extraction quality of the basal ganglia actor network and then updates the weights of its feature *** learning method is proven to converge to the optimal ***,drawing on the mechanism of dopaminergic dynamic regulation in the basal ganglia,the adaptive adjustment of target entropy and the dopaminergic experience replay are proposed to further improve the integration model,which contributes to the exploration-exploitation trade-off of motor *** bio-inspired integration model is validated on a musculoskeletal *** results indicate that this model can effectively control the musculoskeletal robot to accomplish the motion task from random starting locations to random target positions with high precision and robustness.

关键词： Basal ganglia and cerebellum bio-inspired integration model motion learning musculoskeletal robot reinforcement learning.

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Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy

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neural Regeneration research 2024年第3期19卷 680-686页

作者： Jie Wu Yulei Huang Hanrui Yu Kaixiu Li Shifeng Zhang Guoqing Qiao Xiao Liu Hongmei Duan Yifei Huang Kwok-Fai So Zhaoyang Yang Xiaoguang Li Liqiang Wang Department of Ophthalmology the Third Medical CenterChinese PLA General HospitalBeijingChina The PLA Medical College Department of NephrologyChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijingChina Department of Ophthalmology Hainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina Medical School of Chinese PLA BeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Guangdong-Hongkong-Macao institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of brain and Cognitive sciences The University of Hong KongHong Kong Special Administrative RegionChina Center for brain science and brain-Inspired intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina School of Engineering Medicine Beijing Key Laboratory for Biomaterials and Neural RegenerationBeihang UniversityBeijingChina Beijing International Cooperation Bases for science and technology on Biomaterials and neural Regeneration Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang UniversityBeijingChina

Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of *** treatment options for neurotrophic keratopathy are *** this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic *** the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation ***-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in *** denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic *** received topical CTH-mNGF twice daily for 8 *** sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were *** total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were *** 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by ***,six out of seven eyes had fluorescence staining scores<***,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant *** increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven *** study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release *** effecti

关键词： chitosan corneal reinnervation murine nerve growth factor neurotrophic keratopathy thermosensitive hydrogel

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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neural Regeneration research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of Rehabilitation science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina institute of science and technology for brain-Inspired intelligence Fudan UniversityShanghaiChina Key Laboratory of computational Neuroscience and brain-Inspired intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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